Glomerular filtration rate estimation in renal transplant patients based on serum cystatin-C levels: comparison with other markers of glomerular filtration rate


Visvardis, G.; Griveas, I.; Zilidou, R.; Papadopoulou, D.; Mitsopoulos, E.; Kyriklidou, P.; Manou, E.; Ginikopoulou, E.; Meimaridou, D.; Pavlitou, A.; Sakellariou, G.

Transplantation Proceedings 36(6): 1757-1759

2004


The assessment of glomerular filtration rate (GFR) is the most commonly used test of renal function. Cystatin-C, a cysteine protease inhibitor, which can be measured by light-scattering immunoassay, possesses many of the attributes required of the ideal GFR marker. Conversely, many endogenous markers that are widely used for the estimation of GFR such as serum creatinine (SCr) are not ideal. The present study was undertaken to evaluate the clinical application of serum cystatin-C (CysC) as a new marker of GFR in renal transplant patients. Eighteen patients (9 men) were enrolled in the study (mean age: 46.35, range: 31-67 years) to measure serum CysC levels and compare them, with SCr, creatinine clearance (CCr), as well as the Cockcroft-Gault equation (CG) or the MDRD as indicator of GFR. Spearman's correlation coefficient was used to determine the relationship between CysC and other markers. There was a significant negative correlation between serum CysC and CCr (r = -0.768). Moreover, the CysC level was negatively correlated with CG (r = -0.854), positively correlated with SCr (r = 0.629), and negatively correlated with MDRD (r = -0.604). These results indicate that measurement of serum cystatin-C was useful and accurate to estimate GFR in renal transplant patients. The recent literature confirms our data although there are concerns about nonrenal influence on this test. Although serum CysC can generally be recommended as a marker for GFR, our study is still in progress seeking to validate the conclusions in a larger number of patients.

ELSEVIER
Glomerular
Filtration
Rate
Estimation
in
Renal
Transplant
Patients
Based
on
Serum
Cystatin-C
Levels:
Comparison
With
Other
Markers
of
Glomerular
Filtration
Rate
G.
Visvardis,
I.
Griveas,
R.
Zilidou,
D.
Papadopoulou,
E.
Mitsopoulos,
P.
Kyriklidou,
E.
Manou,
E.
Ginikopoulou,
D.
Meimaridou,
A.
Pavlitou,
and
G.
Sakellariou
ABSTRACT
Purpose.
The
assessment
of
glomerular
filtration
rate
(GFR)
is
the
most
commonly
used
test
of
renal
function.
Cystatin-C,
a
cysteine
protease
inhibitor,
which
can
be
measured
by
light-scattering
immunoassay,
possesses
many
of
the
attributes
required
of
the
ideal
GFR
marker.
Conversely,
many
endogenous
markers
that
are
widely
used
for
the
estimation
of
GFR
such
as
serum
creatinine
(SCr)
are
not
ideal.
The
present
study
was
undertaken
to
evaluate
the
clinical
application
of
serum
cystatin-C
(CysC)
as
a
new
marker
of
GFR
in
renal
transplant
patients.
Methods.
Eighteen
patients
(9
men)
were
enrolled
in
the
study
(mean
age:
46.35,
range:
31-67
years)
to
measure
serum
CysC
levels
and
compare
them,
with
SCr,
creatinine
clearance
(CCr),
as
well
as
the
Cockcroft-Gault
equation
(CG)
or
the
MDRD
as
indicator
of
GFR.
Spearman's
correlation
coefficient
was
used
to
determine
the
relationship
between
CysC
and
other
markers.
Results.
There
was
a
significant
negative
correlation
between
serum
CysC
and
CCr
(r
=
—0.768).
Moreover,
the
CysC
level
was
negatively
correlated
with
CG
(r
=
—0.854),
positively
correlated
with
SCr
(r
=
0.629),
and
negatively
correlated
with
MDRD
(r
=
—0.604).
Conclusions.
These
results
indicate
that
measurement
of
serum
cystatin-C
was
useful
and
accurate
to
estimate
GFR
in
renal
transplant
patients.
The
recent
literature
confirms
our
data
although
there
are
concerns
about
nonrenal
influence
on
this
test.
Although
serum
CysC
can
generally
be
recommended
as
a
marker
for
GFR,
our
study
is
still
in
progress
seeking
to
validate
the
conclusions
in
a
larger
number
of
patients.
C
YSTATIN-C
(CysC),
a
low-molecular-weight
(13
kDa)
protease
inhibitor,
has
recently
gained
the
interest
of
the
scientific
community
as
an
alternative
and
more
reliable
marker
of
glomerular
filtration
rate
(GFR).'
Its
low
molec-
ular
weight
and
positive
charge
at
physiological
pH
allow
easy
passage
through
the
glomerular
filter;
however,
it
is
reabsorbed
in
the
proximal
tubules
and
catabolized,
thus
explaining
the
low
levels
in
normal
urine.'
The
present
study
was
undertaken
to
evaluate
the
clinical
application
of
serum
CysC
as
a
new
marker
of
GFR
in
renal
transplant
patients.
PATIENTS
AND
METHODS
Eighteen
renal
transplant
patients
(9
men)
were
enrolled
in
the
present
study
(mean
age:
46.35
years,
range:
31-67
years).
All
patients
had
stable
renal
function
for
the
last
6
months
without
any
©
2004
by
Elsevier
Inc.
All
rights
reserved.
360
Park
Avenue
South,
New
York,
NY
1
001
0-1
71
0
changes
in
immunosuppressive
agents
for
at
least
4
weeks.
We
measured
CysC
levels
by
particle
enhanced
tubidimetric
method
to
compare
them
with
serum
creatinine
(SCr),
creatinine
clearance
(CCr),
Cockcroft-Gault
(CG)
formula:
[(140-age)
X
weight/72
X
Cr]
X
(0.85
if
female)
and
with
Modification
of
Diet
in
Renal
Disease
(MDRD)
study
equation:
186
X
(Cr)
-1-154
X
(age)
-0.203
X
(0.742
if
female),
as
markers
of
estimation
of
GFR.
Spearman's
correlation
coefficients
(SPSS
Version
10)
were
used
to
determine
the
above
relationships.
From
the
Nephrology
Department,
Papageorgiou
General
Hospital,
and
Immunology
Department,
Papageorgiou
General
Hospital,
Thessaloniki,
Greece.
Address
reprint
requests
to
George
Visvardis,
Nephrology
Department,
Papageorgiou
General
Hospital,
N.
Efkarpia,
Ring
Road,
Thessaloniki,
Greece.
E-mail:
0041-1345/04/$-see
front
matter
doi:10.1016/j.transproceed.2004.06.009
Transplantation
Proceedings,
36,
1757-1759
(2004)
1757
4,0
3,5.
3,0
2,5
2,0
1,5
1,0
.
5
00
1,0
1,5
2,0
CYS
Fig
3.
Correlation
between
serum
CysC
and
Cr.
2,5
120
100
80
60•
40•
20
00
,5
1,0
1:5
2,0
25
120
100
80
60
40
❑❑
20
1758
VISVARDIS,
GRIVEAS,
ZILIDOU
ET
AL
CYS
Fig
1.
Correlation
between
serum
CysC
and
CCr.
RESULTS
A
significant
negative
correlation
existed
between
serum
CysC
and
CCr
(r
=
—0.768)
(P
<
.01)
(Fig
1).
Moreover,
the
CysC
level
was
negatively
correlated
with
CG
(r
=
—0.854)
(P
<
.01)
(Fig
2),
positively
correlated
with
SCr
(r
=
0.629)
(P
<
.05)
(Fig
3),
and
negatively
correlated
with
MDRD
(P
<
.05)
(r
=
—0.604)
(Fig
4).
DISCUSSION
Measurement
of
GFR
is
essential
to
estimate
renal
function
among
renal
transplant
patients.
The
GFR
is
a
marker
that
determines
the
severity
of
injury
and
is useful
to
follow
renal
injury.
In
everyday
clinical
practice,
CCr,
the
CG
formula,
and
the
MDRD
equation
are
used
to
estimate
GFR.
3
However,
they
are
not
ideal,
and
therefore
not
accurate,
if
we
consider
that
they
based
on
the
level
of
SCr.
Conversely,
CysC,
a
universal
inhibitor
of
cysteine
pro-
tease,
has
gained
the
interest
of
the
scientific
community.
Cysteine
proteases
are
proteolytic
enzymes
found
in
the
120
100
80
60
40
20
lysosomes
of
cells
and
involved
in
many
pathological
pro-
cesses.
The
role
of
cysteine
proteases
is
crucial
to
normal
cellular
metabolism,
being
fundamental
for
intracellular
protein
turnover,
degradation
of
collagen,
and
cleavage
of
precursor
proteins.'
The
diagnostic
accuracy
of
the
particle-
enhanced
tubidimetric
method
is
superior
to
that
of
routine
creatinine
methods.
4
Normal
values
depending
on
age
are:
20
to
50
years:
0.70
to
1.21
mg/dL;
>50
years:
0.84
to
1.55
mg/dL.
8
In
the
present
study,
levels
of
CysC
were
correlated
with
SCr,
CCr,
the
CG
formula,
and
the
MDRD
equation
as
markers
of
GFR.
There
was
a
statistically
significant
posi-
tive
correlation
between
CysC
and
SCr.
There
was
also
a
good
correlation
between
CysC
and
CCr,
the
CG
formula,
and
the
MDRD
equation.
Our
findings
confirmed
the
recent
literature
6
7
reporting
CysC
as
an
accurate
early
marker
of
renal
injury:
7
'
8
In
conclusion,
CysC
is
an
easy,
precise
marker
to
estimate
GFR.
It
is
also
sensitive
owing
to
proven
technology
and
does
not
show
interference
from
other
parameters
(muscle
0.
0
O
0,0
1,0
1,5
2,0
2,5
00
,5
1,0
1,5
2,0
25
CYS
CYS
Fig
2.
Correlation
between
serum
CysC
and
CG.
Fig
4.
Correlation
between
serum
CysC
and
MDRD.
GLOMERULAR
FILTRATION
RATE
1759
mass,
incorrect
collection
of
24-hour
urine
output).
To
realize
the
full
diagnostic
potential
of
CysC,
more
research
needs
to
be
performed
on
the
interaction
of
all
cystatin
species
found
in
biological
fluids,
as
well
as
the
regulatory
mechanisms
that
control
their
production.
A
larger
number
of
renal
transplant
patients
is
needed
to
confirm
our
findings
and
to
reveal
the
prognostic
value
of
CysC
for
assessing
renal
damage.
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